Modulation of genomic and postgenomic alterations in noncancer diseases and critical periods of life.
Genomic and postgenomic changes are extensively investigated in cancer research. Similar alterations, affecting genome, transcriptome, mirnome and/or proteome end-points, have been detected in a variety of other chronic degenerative diseases, such as atherosclerosis, degenerative heart diseases, chronic obstructive pulmonary diseases, neurological disorders, eye diseases, diabetes, metabolic syndrome, skin ageing and alopecia. No generalization can be made due to the myriad of diverse clinical entities classified as chronic degenerative diseases. Moreover, the detection of molecular changes does not automatically imply their causal role. Nevertheless, common mechanisms, such as DNA damage, epigenetic alterations, oxidative stress, and chronic inflammation, in addition to genetic predisposition, are often involved in noncancer diseases. We debate here in more detail the subjects of cardiovascular diseases and of skin diseases. Moreover, we discuss our experimental studies suggesting that genomic and postgenomic changes do also occur during critical periods of life, including the prenatal life, the perinatal period, and ageing. In addition, we comment on the finding that stem-derived cells are more susceptible to molecular damage than more differentiated cells. All these data are viewed in the perspective of preventive medicine. In fact, there is evidence that the genomic and postgenomic alterations occurring not only in several pathological conditions but also in paraphysiological situations that affect critical periods of life can be modulated by means of dietary and pharmacological agents. The discovery that chemopreventive agents are also able to attenuate nucleotide damage in stem-derived cells warrants further studies in view of possible clinical applications.
De Flora
Silvio
S
Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy. sdf@unige.it
Izzotti
Alberto
A
D000375:Aging; D000818:Animals; D002908:Chronic Disease; D004249:DNA Damage; D004272:DNA, Mitochondrial; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange; D011247:Pregnancy
D004272:DNA, Mitochondrial